Background Leptin, the product of the ob gene, is a hormone secreted by adipocytes. Animals with mutations in the ob gene are obese and lose weight when given leptin, but little is known about the physiologic actions of leptin in humans. Methods Using a newly developed radioimmunoassay, we measured serum concentrations of leptin in 136 normal-weight subjects and 139 obese subjects (body-mass index, >27.3 for men and >27.8 for women; the body-mass index was defined as the weight in kilograms divided by the square of the height in meters). The measurements were repeated in seven obese subjects after weight loss and during maintenance of the lower weight. The ob messenger RNA (mRNA) content of adipocytes was determined in 27 normal-weight and 27 obese subjects. Results The mean (±SD) serum leptin concentrations were 31.3±24.1 ng per milliliter in the obese subjects and 7.5±9.3 ng per milliliter in the normal-weight subjects (P<0.001). There was a strong positive correlation between serum leptin concentration...

Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans

New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its importance to human health. Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity, the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process. To better understand how energy homeostasis can be achieved, we describe a model that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from inherited or acquired defects in their function.

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Central nervous system control of food intake

The assimilation, storage and use of energy from nutrients constitute a homeostatic system that is essential for life In vertebrates, the ability to store sufficient quantities of energy-dense triglyceride in adipose tissue allows survival during the frequent periods of food deprivation encountered during evolution However, the presence of excess adipose tissue can be maladaptive A complex physiological system has evolved to regulate fuel stores and energy balance at an optimum level Leptin, a hormone secreted by adipose tissue, and its receptor are integral components of this system Leptin also signals nutritional status to several other physiological systems and modulates their function Here we review the role of leptin in the control of body weight and its relevance to the pathogenesis of obesity

Leptin and the regulation of body weight in mammals

https://www.cell.com/cell/pdf/S0092-8674(00)80949-6.pdf

Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

Identification and expression cloning of a leptin receptor Ob-R

Recently Zhang et al. cloned a gene that is expressed only in adipose tissue of the mouse. The obese phenotype of the ob/ob mouse is linked to a mutation in the obese gene that results in expression of a truncated inactive protein. Human and rat homologues for this gene are known. Previous experiments predict such a hormone to have a hypothalamic target. Hypothalamic neuropeptide Y stimulates food intake, decreases thermogenesis, and increases plasma insulin and corticosterone levels making it a potential target. Here we express the obese protein in Escherichia coli and find that it suppresses food intake and decreases body weight dramatically when administered to normal and ob/ob mice but not db/db (diabetic) mice, which are thought to lack the appropriate receptor. High-affinity binding was detected in the rat hypothalamus. One mechanism by which this protein regulated food intake and metabolism was inhibition of neuropeptide-Y synthesis and release.

Julie M Bue-Valleskey

Papers

The role of neuropeptide Y in the antiobesity action of the obese gene product.

Regulation of Expression of ob mRNA and Protein by Glucocorticoids and cAMP

Use of insulin lispro (Humalog®) mixtures in the elderly provides comparable safety to that of human insulin mixtures